Journal article Open Access

The Story about the constructed SARS COV-2 Virus - A Review of three Research Groups




A literature research on synthetic recombinant SARS Coronavirus was made to answer two questions. Is the SARS CoV-2 virus designed in a laboratory? And why has the SARS CoV-2 such a high mutation rate? A total of 12 research articles, 2 reviews and 10 experimental studies were attributed to three Research Groups, the Wadsworth Center New York, the Vanderbilt Medical Center, and the Chapel Hill North Carolina. The research papers were published between 1991 and 2014. All 12 research papers reported the successful construction of recombinant SARS Coronaviruses based on RNA reverse genetic and molecular techniques. The Research group from the Medical Center at Vanderbilt University proved how an engineered SARS Coronavirus with an impaired Exonuclease resulted in a progeny virus with high mutation rate. Furthermore, the review showed that a zoonotic-human transmission was just possible with specific genetic manipulations at the SARS CoV virus genome through selection of virus species for recombination, and targeted manipulation at non-structural virus domains. But importantly, the studies showed that a SARS Coronavirus cross-species infection such as between zoonotic and humans or between different animal species without the exchange of the virus spike protein domain with the host-specific receptor-binding domain (RBD) and additional point mutations was not possible. Therefore, the SARS CoV-2 was deliberately constructed to overcome the receptor limiting factor for animal-human infection. Interestingly, the review revealed that the study purpose of constructed recombinant SARS CoV changed from the scientific research point of view to vaccine production and development. Competing interests for all reviewed studies by grants from private investors such as the Gates Foundation and vaccine production companies were part of the discussion. Keywords: SARS CoV-2, Covid19, Spike protein, gene sequencing, Vanderbilt University, University North Carolina, Wadsworth Research Center, New York Health Department, Coronavirus, Bill & Melinda Gates Foundation, WHO, Pfizer, Merck, Novartis, AlphaVax

The author declares no competing interests.
Files (123.0 kB)
Name Size
The Story about the constructed SARS COV-2 Virus.pdf
123.0 kB Download
  • Paul. S. Masters, Peter J. M. Rottier. Coronavirus Reverse Genetics by Targeted RNA Recombination. Springer-Verlag.2005;287:133-159

  • Cornelis A.M. de Haan, Bert Jan Haijema, Paul S. Masters, Peter J.M. Rottier. Manipulation of the Coronavirus Genome Using Targeted RNA Recombination with Interspecies Chimeric Coronaviruses. Methods Mol Biology.2008;454: 229-236.

  • Michelle M. Becker, Rachel L.Graham, Eric F. Donaldson, Barry Rockx, Amy C. Sims, Timothy Sheahan, Raymond J. Pickles, Davide Corti, Robert E. Johnston, Ralph S. Baric, Mark R. Denison. Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice. PNAS.2008;105(50): 19944-19949.

  • Cheri A. Koetzner, Monica M. Parker, Cynthia S. Ricard, Lawrence S.Sturman, Paul S. Masters. Repair and Mutagenesis of the Genome of a Deletion Mutant of the Coronavirus Mouse Hepatitis Virus by Targeted RNA Recombination. Journal of Virology.1992:66(4): 1841-1848.

  • Lili Kuo, Gert-Jan Godeke, Martin J. B. Raamsman, Paul S. Masters, Peter J. M. Rottier. Retargeting of Coronavirus by Substitution of the Spike Glycoprotein Ectodomain: Crossing the Host Cell Species Barrier. Journal of Virology.2000;74(3): 1393-1406.

  • Erik Prentice, Mark R. Denison. The Cell Biology of Coronavirus Infection. Adv. Exp Med Biol.2001;494: 609-614.

  • Rachel L. Graham, Amy C. Sims, Ralph S. Baric, and Mark R. Denison. The NSP2 Proteins of mouse Hepatitis Virus and SARS Coronavirus are dispensable for viral replication. Adv. Exp Med Biol. 2006;581: 67-72.

  • Lance D. Eckerle , Michelle M. Becker, Rebecca A. Halpin, Kelvin Li, Eli Venter, Xiaotao Lu, Sana Scherbakova, Rachel L.Graham, Ralph S. Baric, Timothy B. Stockwell, David J. Spiro, Mark R. Denison. Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing. PLoS Pathogens.2010;6(5).

  • Mark J. Gadlag, Mark R. Denison. Exchange of the Coronavirus Replicase Polyprotein Cleavage Sites Alters Protease Specificity and Processing. Journal of Virology. 2010;84(13): 6894-6898.

  • Barry Rockx, Timothy Sheahan, Eric Donaldson, Jack Harkema, Amy Sims, Mark Heise, Raymond Pickles, Mark Cameron, David Kelvin, Ralph Baric. Synthetic Reconstruction of Zoonotic and Early Human Severe Acute Respiratory Syndrome Coronavirus Isolates That Produce Fatal Disease in Aged Mice. Journal of Virology.2007;81(14): 7410-7423.

  • Timothy Sheahan, Barry Rockx, Eric Donaldson, Davide Corti, Ralph Baric. Pathways of Cross-Species Transmission of Synthetically Reconstructed Zoonotic Severe Acute Respiratory Syndrome Coronavirus. Journal of Virology.2008;82(17): 8721-8732.

  • Sudhakar Agnihothram, Boyd L. Yount, Jr.,Eric F. Donaldson, Jeremy Huynh, Vineet D. Menachery, Lisa E. Gralinski, Rachel L. Graham, Michelle M. Becker, Sakshi Tomar, Trevor D. Scobey, Heather L. Osswald, Alan Whitmore, Robin Gopal, Arun K. Ghosh, Andrew Mesecar, Maria Zambon, Mark Heise, Mark R. Denison, Ralph S. Baric. A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant. Mbio.2014;5(2).

  • Wikipedia. Global Vaccines Inc. 2018. [accessed 25/02/2021 ]

  • Lin-Fa Wang, Zhengli Shi, Shuyi Zhang, Hume Field,Peter Daszak, and Bryan T. Eaton, Review of Bats and SARS. Emerging Infectious Diseases. 2006;12.

  • Cornelis A. M. de Haan, Paul S. Masters, Xiaolan Shen, Susan Weiss, Peter J. M. Rottier. The Group-Specific Murine Coronavirus Genes Are Not Essential, but Their Deletion, by Reverse Genetics, Is Attenuating in the Natural Host. Virology.2002;296:177-189.

  • Biotechnology Innovation Organisation. Companies Researching Diseases of Developing Nations <br>To Present at Gates Foundation/BIO Global Health Forum. [accessed 26/02/2021 ]

  • LinkedIn. Robert Johnston. [accessed 26/02/2021 ]

  • The Association of American Universities. Comparing Foundations to Federal Government Research Support; [accessed 25/02/2021 ]

  • Damon Deming, Timothy Sheahan, Mark Heise, Boyd Yount, Nancy Davis, Amy Sims, Mehul Suthar, Jack Harkema, Alan Whitmore, Raymond Pickles, Ande West, Eric Donaldson, Kristopher Curtis, Robert Johnston, Ralph Baric. Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants. PloS Medicine.2006;3(12): e525

  • Federal employee profile-Michelle M. Becker.2021; [accessed 25/02/2021 ]

  • Gates Foundation. Awarded Grants NIH 2013; [accessed 26/02/2021 ]

  • Gates Foundation. Awarded Grants.NIH; [accessed 26/02/2021 ]

  • . Vanderbilt University. Corporate and Foundation relations. 2021; [accessed 26/02/2021]

  • Gates Foundation. Awarded Grants.Vanderbilt University; [accessed 01/02/2021 ]

  • Gates Foundation. Awarded Grants. Chapel Hill. [accessed 26/02/2021 ]

  • The World Health Organization. Eastern Mediterranean Health Journal. [accessed 26/02/2021 ]

  • "What is the purpose of medical research?" Editorial. The Lancet. February 2, 2013;381:347.Print

All versions This version
Views 573573
Downloads 267267
Data volume 32.8 MB32.8 MB
Unique views 518518
Unique downloads 250250


Cite as